4x9n

From Proteopedia

(Difference between revisions)

Current revision

Dithionite reduced L-alpha-Glycerophosphate Oxidase from Mycoplasma pneumoniae with FAD bound

Structural highlights

4x9n is a 1 chain structure with sequence from Mycoplasma pneumoniae M129. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.499Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GLPO_MYCPN Catalyzes the oxidation of glycerol 3-phosphate to dihydroxyacetone phosphate (DHAP), with a reduction of O2 to H2O2. The formation of hydrogen peroxide by this enzyme is crucial for cytotoxic effects of M.pneumoniae on host cells. Is involved in the metabolism of glycerol and is essential for glycerol utilization; glycerol is one of the few carbon sources that can be utilized by M.pneumoniae for growth (PubMed:19028882). To a lesser extent, is also able to use glyceraldehyde 3-phosphate (GAP), an intermediate in the glycolysis pathway, as a substrate (but the structure of the product has not been elucidated). Therefore, in the absence of glycerol, GAP may serve as a substrate in the GlpO reaction to supply H2O2 during mycoplasma infection (PubMed:25712468). Does not show any dehydrogenase activity with NAD(+) (PubMed:19028882).^[1] ^[2]

Publication Abstract from PubMed

The formation of hydrogen peroxide (H2 O2 ) by the FAD-dependent alpha-glycerophosphate oxidase (GlpO), is important for the pathogenesis of Streptococcus pneumoniae and Mycoplasma pneumoniae. The structurally known GlpO from Streptococcus sp. (SspGlpO) is similar to the pneumococcal protein (SpGlpO) and provides a guide for drug design against that target. However, M. pneumoniae GlpO (MpGlpO), having <20% sequence identity with structurally known GlpOs, appears to represent a second type of GlpO we designate as Type II GlpOs. Here, the recombinant His-tagged MpGlpO structure is described at ~2.5 A resolution, solved by molecular replacement using as a search model the Bordetella pertussis protein 3253 (Bp3253) a protein of unknown function solved by structural genomics efforts. Recombinant MpGlpO is an active oxidase with a turnover number of ~580 min-1 while Bp3253 showed no GlpO activity. No substantial differences exist between the oxidized and dithionite-reduced MpGlpO structures. Although, no liganded structures were determined, a comparison with the tartrate-bound Bp3253 structure and consideration of residue conservation patterns guided the construction of a model for alpha-glycerophosphate (Glp) recognition and turnover by MpGlpO. The predicted binding mode also appears relevant for the type I GlpOs (such as SspGlpO) despite differences in substrate recognition residues, and it implicates a histidine conserved in type I and II Glp oxidases and dehydrogenases as the catalytic acid/base. This work provides a solid foundation for guiding further studies of the mitochondrial Glp dehydrogenases as well as for continued studies of M. pneumoniae and S. pneumoniae glycerol metabolism and the development of novel therapeutics targeting MpGlpO and SpGlpO. This article is protected by copyright. All rights reserved.

Structure and proposed mechanism of alpha-glycerophosphate oxidase from Mycoplasma pneumoniae.,Elkhal CK, Kean K, Parsonage D, Maenpuen S, Chaiyen P, Claiborne A, Karplus PA FEBS J. 2015 Feb 16. doi: 10.1111/febs.13233. PMID:25688572^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hames C, Halbedel S, Hoppert M, Frey J, Stülke J. Glycerol metabolism is important for cytotoxicity of Mycoplasma pneumoniae. J Bacteriol. 2009 Feb;191(3):747-53. PMID:19028882 doi:10.1128/JB.01103-08
↑ Maenpuen S, Watthaisong P, Supon P, Sucharitakul J, Parsonage D, Karplus PA, Claiborne A, Chaiyen P. Kinetic mechanism of L-α-glycerophosphate oxidase from Mycoplasma pneumoniae. FEBS J. 2015 Aug;282(16):3043-59. PMID:25712468 doi:10.1111/febs.13247
↑ Elkhal CK, Kean K, Parsonage D, Maenpuen S, Chaiyen P, Claiborne A, Karplus PA. Structure and proposed mechanism of alpha-glycerophosphate oxidase from Mycoplasma pneumoniae. FEBS J. 2015 Feb 16. doi: 10.1111/febs.13233. PMID:25688572 doi:http://dx.doi.org/10.1111/febs.13233

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4x9n"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4x9n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycoplasma_pneumoniae_M129 Mycoplasma pneumoniae M129]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X9N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X9N FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.499&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4x9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x9n OCA], [https://pdbe.org/4x9n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x9n RCSB], [https://www.ebi.ac.uk/pdbsum/4x9n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x9n ProSAT]</span></td></tr>
 </table>

4x9n

From Proteopedia

Current revision

Dithionite reduced L-alpha-Glycerophosphate Oxidase from Mycoplasma pneumoniae with FAD bound

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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